The object of the proposed investigation is to study the biochemical parameters of the genetic neurological disorder metachromatic leukodystrophy (MLD). MLD is a group of disorders including the classical forms, late infantile, juvenile and adult, multiple sulfatase deficiency disorder, and different clinically and biochemically atypical forms. In each of these forms, there is a defect in the lysosomal enzyme arylsulfatase A which results in pertubations in the catabolism of the myelin constituent cerebroside sulfate. The primary experimental model is fibroblasts in culture derived from patients with various forms of MLD. All MLD fibroblast strains synthesize an arylsulfatase A gene product (mutant enzyme) and depending on the form of the disorder they vary from no catalytic activity to experimentally significant activity. Various enzymatic and physico-chemical properties of mutant enzymes will be examined in an effort to define specific properties which differ from those of normal arylsulfatase A. In parallel studies, properties of the enzyme in growing MLD fibroblasts will be examined, also in an effort to define those which are at variance from the normal enzyme. They will include synthesis, maturation, intracellular location and turnover.